Low-temperature-field-assisted fabrication of cross-scale tissue engineering scaffolds

Abstract In tissue engineering (TE), tissue-inducing scaffolds are a promising solution for organ and tissue repair owing to their ability to attract stem cells in vivo , thereby inducing endogenous tissue regeneration through topological cues. An ideal TE scaffold should possess biomimetic cross-scale structures, similar to that of natural extracellular matrices, at the nano- to macro-scale level. Although freeform fabrication of TE scaffolds can be achieved through 3D printing, this method is limited in simultaneously building multiscale structures. To address this challenge, low-temperature fields were adopted in the traditional fabrication processes, such as casting and 3D printing. Ice crystals grow during scaffold fabrication and act as a template to control the nano- and micro-structures. These microstructures can be optimized by adjusting various parameters, such as the direction and magnitude of the low-temperature field. By preserving the macro-features fabricated using traditional methods, additional micro-structures with smaller scales can be incorporated simultaneously, realizing cross-scale structures that provide a better mimic of natural organs and tissues. In this paper, we present a state-of-the-art review of three low-temperature-field-assisted fabrication methods—freeze casting, cryogenic 3D printing, and freeze spinning. Fundamental working principles, fabrication setups, processes, and examples of biomedical applications are introduced. The challenges and outlook for low-temperature-assisted fabrication are also discussed.